DESCRIPTION: (Applicant's Abstract) Both genetic and environmental factors play important roles in the etiology of psychoactive substance use disorders (PSUD). However, our knowledge of the relative importance of these risk factors and how they interrelate in the US population remains limited. We propose a comprehensive, 3-phase twin and twin-family study in the birth-certificate based Virginia Twin Registry (VTR) focusing on 5 substances of abuse: nicotine, caffeine, cannabis, cocaine and stimulants: Phase 1 will consist of analyses of data collected with NIDA support on PSUD in 3,300 personally interviewed unselected female-female, male-male and male-female adult twin pairs from the VTR, with the aim of quantifying the role of genetic, individual-specific environmental and familial-environmental factors in the etiology of substance use, abuse and dependence and clarifying the degree to which these risk factors are similar for different substances and for men and women. In phase 2, we will complete new interviews, focusing on PSUD and its risk factors, with all cooperative members of the male-male twin pairs from this sample (n=2,760) and their parents (n=2,000), measuring twin PSUD on two occasions, utilizing a life history calendar, assessing key risk factor domains from multiple informants and obtaining school and criminal records on all informants. In phase 3, we will examine a series of questions using the complete data set of twins and twins with parents. Analyses to be performed include: i) re-assessing the role of genetic and environmental risk factors in substance use, PSUD, and individual forms of PSUD, using data from multiple occasions and informants, ii) exploring a range of univariate and multi variate twin-family models to clarify the mechanism of the cross-generational transmission of the vulnerability to PSUD, iii) using multi variate twin modeling to clarify the genetic and environmental sources of covariation between substance use and PSUD and psychiatric illness, alcoholism and a range of putative risk factors including temperament, childhood behavioral dysregulation and adolescent peer group deviancy, iv) determining the nature of the interaction between genetic and environmental risk factors for substance use and PSUD and v) developing statistically rigorous, comprehensive etiologic models for PSUD.